Anti-obesity effects of long-chain omega-3 polyunsaturated fatty acids

Animal studies suggest that increased consumption of the long-chain omega-3 polyunsaturated fatty acids, eicosapentaenoic acid and docosahexaenoic acid, can protect against the development of obesity in animals exposed to an obesogenic diet and reduce body fat when already obese. There is also evidence that increased intakes of these fatty acids can reduce body fat in humans, but human studies are relatively few and have generally been conducted over short time periods with small sample sizes, making it difficult to draw definitive conclusions. Reported reductions in body fat may result from appetite-suppressing effects, adipocyte apoptosis and changes of gene expression in skeletal muscle, heart, liver, intestine and adipose tissues that suppress fat deposition and increase fat oxidation and energy expenditure. We conclude that increased intakes of long-chain omega-3 fatty acids may improve body composition, but longer-term human studies are needed to confirm efficacy and determine whether increasing omega-3 intakes might be an effective strategy to combat obesity.     

Effect of butyrate on paracellular permeability in rat distal colonic mucosa ex vivo

BACKGROUND AND AIMS: The effects of butyrate on colonic epithelial barrier function are poorly understood. The aim of this study was to examine the short-term effects of butyrate on paracellular permeability of rat distal colonic epithelium. METHODS: Mucosa mounted in Ussing chambers was treated with butyrate (1-10 mmol/L) for 4 h. Transepithelial conductance, [51Cr]-EDTA flux, mucosal brush border hydrolase activity and epithelial kinetics, using proliferating cell nuclear antigen (PCNA) staining, were measured. RESULTS: On exposure to butyrate (10 mmol/L, but not 1 or 5 mmol/L), transepithelial conductance was 65 +/- 2% higher (mean +/- SEM; n = 8, P < 0.05, paired t-test) and the rate coefficient for [51Cr]-EDTA flux was 65 +/- 25% higher (P = 0.03) than those of control tissue. Histologically, the epithelium exhibited no signs of injury, but butyrate-treated tissue exhibited interstitial oedema consistent with water uptake in association with butyrate absorption. Butyrate caused a reduction in crypt column height to 30.6 +/- 1.6 cells from 33.4 +/- 1.8 cells in controls (n = 10, P < 0.03), but the number of cells per crypt column staining with PCNA was unchanged. Butyrate significantly reduced the mucosal activities of alkaline phosphatase by 40 +/- 16%, maltase by 54 +/- 12% and dipeptidyl peptidase IV by 41 +/- 14%. CONCLUSIONS: Acute exposure to butyrate increased paracellular permeability in rat distal colon. The mechanism involved may relate to the loss of differentiated surface epithelial cells, or as a physiological response to Na+-coupled butyrate uptake.     

Polyunsaturated fatty acid intake and blood pressure in adolescents

Evidence that intake of polyunsaturated fatty acids (PUFAs) may modify blood pressure (BP) is generally limited to middle-aged or hypertensive populations. This study examined cross-sectional associations between BP and dietary intake of PUFAs in 814 adolescents aged 13-15?years participating in the Western Australian Pregnancy Cohort (Raine) Study. Fatty acid intakes were assessed using 3-day diet records and resting BP was determined using multiple oscillometric readings. In multivariate regression models, systolic BP was inversely associated with intakes of polyunsaturated (b=-0.436, P<0.01), omega-3 (b=-2.47, P=0.02), omega-6 (b=-0.362, P=0.04) and long chain omega-3 fatty acids (b=-4.37, P=0.04) in boys. Diastolic BP and mean arterial pressure were inversely associated with intakes of long chain omega-3 fatty acids in boys (b=-3.93, P=0.01, b=-4.05, P=0.01, respectively). For specific long-chain omega-3s, significant inverse associations were observed between eicosapentaenoic acid (EPA) and docosahexaenoic acid, such as systolic BP decreasing by 4.7?mm?Hg (95% CI -9.3 to -0.1) for a quarter gram increase in EPA, but no significant associations were observed with docosapentaenoic acid. No significant associations were observed in girls, or with the omega-6 to omega-3 ratio. Our results suggest that gender may moderate relationships between fatty acid intake and BP in adolescence.     

The effects of fatty acids on apolipoprotein B secretion by human hepatoma cells (HEP G2)

We have investigated the effect of fatty acids on the rate of apolipoprotein B (apo B) secretion by human hepatoma cells (Hep G2). When Hep G2 cells were maintained in tissue culture flasks oleic acid up to 0.4 mM increased apo B secretion in a dose-dependent manner, whereas increases in triacylglycerol (TG) were smaller and dose dependency was less evident. In the absence of oleic acid, apo B accumulating in the tissue culture medium was predominantly in lipoproteins of higher density than very low density lipoproteins (VLDL). However, when the rate of secretion was stimulated with oleic acid the apo B-containing lipoproteins became lower in density. We postulated that there was a high rate of lipolysis of newly secreted VLDL by Hep G2 cells, which would account both for the relatively smaller effect of oleic acid on TG as opposed to apo B accumulating in the culture medium and the predominance of apo B in lipoproteins of a higher density than VLDL, which became less evident when VLDL secretory rates were stimulated by oleic acid. To test this hypothesis, cultured Hep G2 cells were transferred to columns containing Cytodex beads, permitting their continuous perfusion with culture medium so that newly secreted VLDL did not remain in contact with the cells. Apo B recovered from the perfusate was largely in VLDL range lipoproteins and the TG measured in the perfusate indicated that the true secretory rate of TG-rich lipoproteins was substantially higher than had been reflected by TG accumulating in culture medium left in contact with cells. Apo B measured in the culture medium of Hep G2 cells may thus be a better reflection of VLDL secretion, even though it is contained in higher density lipoproteins due to removal of TG by lipolysis. The effects of saturated fatty acids (SFA), monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) on apo B (apo B) secretion by Hep G2 cells maintained in tissue culture flasks were next investigated. SFA (0.4 mM), with the exception of stearic acid (C18:0), increased apo B secretion. Lauric acid (C12:0) increased apo B secretion by 32%, myristic acid (C14:0) by 41% (P<0.005), palmitic acid (C16:0) by 154% (P<0.025), and arachidic acid (C20:0) by 186% (P<0.005). The effect of MUFA (0.4 mM) was to increase apo B secretion, oleic acid (C18:1) by 239% ((P<0.0005) and palmitoleic acid (C16: 1) by 125% (P<0.005). Of the PUFA investigated, linolenic acid (C18:3) (0.4 mM) did not have any significant effect on apo B secretion, whereas linoleic acid (C18:2) (0.4mM) arachidonic acid (C20:4) (0.1 mM) and eicosapentaenoic acid (C20:5) (0.1 mM) caused significant increases of 164, 171 and 171%, respectively (P<0.005). The fatty acids studied increased intracellular TG and cholesteryl ester concentrations to varying extents. The increase in intracellular TG produced by the different fatty acids correlated with the rate of apo B secretion (r=0.6; P<0.05). In this human hepatoma cell line, with the exception of the saturated fatty acids, the rate of secretion of apo B-containing lipoproteins does not follow the same pattern as changes in circulating low density lipoprotein (LDL) concentrations reported with dietary manipulation in man. If our findings reflect the in vivo situation, we suggest that whilst the dietary effects of SFA on serum LDL may in part be determined by the hepatic apo B secretory rate, the effects of MUFA and PUFA must be largely mediated through a catabolic effect rather than an effect on hepatic secretion. The marked increase in apo B secretion with the more highly polyunsaturated fatty acids, such as eicosapentaenoic acid, may also explain why they do not lower circulating LDL, despite reports of their apparently favourable effect on LDL-receptor mediated clearance.     

Platelet function, thromboxane formation and blood pressure control during supplementation of the Western diet with cod liver oil

Epidemiologic and experimental data suggest an antiatherothrombotic potential of omega-3 polyunsaturated fatty acids. Therefore, the Western diet, which supplies predominantly omega-6 polyunsaturated fatty acids, was supplemented with 40 ml/day of cod liver oil, which provides about 10 g of omega-3 polyunsaturated fatty acids daily, for 25 days in eight volunteers. The omega-3 polyunsaturated fatty acids were incorporated in platelet and erythrocyte membrane phospholipids at the expense of omega-6 polyunsaturated fatty acids. Bleeding time increased (p less than 0.01) and platelet count (p less than 0.05), platelet aggregation upon ADP and collagen (p less than 0.01-0.05), and associated thromboxane B2 formation (p less than 0.01) decreased. Blood pressure (p less than 0.05) and blood pressure response to norepinephrine (p less than 0.01) and angiotensin II (NS) fell, without major changes in plasma catecholamines, renin, urinary aldosterone, kallikrein, prostaglandins E2 and F2 alpha and red cell cation fluxes. Biochemical and functional changes were reversed 4 weeks after cod liver oil was discontinued. Formation of prostaglandins derived from eicosapentaenoic acid and interference of eicosapentaenoic acid with formation and action of prostaglandins derived from arachidonic acid were evident in vitro. Whatever the mechanism, this moderate supplement of omega-3 polyunsaturated fatty acids markedly changed membrane phospholipids, which was associated with a shift toward less reactive platelets and a blunted circulatory response to pressure hormones.     

Omega-3 fatty acids improve blood pressure control and preserve renal function in hypertensive heart transplant recipients.

BACKGROUND: Hypertension and cyclosporine-induced nephrotoxicity are common complications in heart transplant recipients. Omega-3 fatty acids may prevent blood pressure rise early, but have not been studied long-term after heart transplantation. METHODS AND RESULTS: Forty-five clinically stable hypertensive heart transplant recipients were studied 1-12 years after transplantation and randomized in a double-blind fashion to receive either 3.4 g of omega-3 fatty acids daily or placebo for 1 year. Ambulatory 24 h blood pressure monitoring and haemodynamic studies were performed before randomization and at the end of the study. Systolic blood pressure increased by 8+/-3 mmHg (P<0.01) in the placebo group, with a non-significant increase in diastolic blood pressure of 3+/-2 mmHg (P=0.10), accompanied by a 14% increase in systemic vascular resistance (P<0.05). In contrast, no change in blood pressure or systemic vascular resistance was recorded in the omega-3 group. Plasma creatinine increased (P<0.01) and glomerular filtration rate decreased (P<0.05) in the placebo group, while no changes were observed in the omega-3 group. The antihypertensive effect was related to an increase in serum eicosapentaenoic and docosahexaenoic acid. CONCLUSION: Treatment with omega-3 fatty acids may reduce the long-term continuous rise in blood pressure after heart transplantation and may offer a direct or indirect renoprotective effect, making these fatty acids a potentially attractive treatment for post-transplant hypertension.     

Free, long-chain, polyunsaturated fatty acids reduce membrane electrical excitability in neonatal rat cardiac myocytes.

Because previous studies showed that polyunsaturated fatty acids can reduce the contraction rate of spontaneously beating heart cells and have antiarrhythmic effects, we examined the effects of the fatty acids on the electrophysiology of the cardiac cycle in isolated neonatal rat cardiac myocytes. Exposure of cardiomyocytes to 10 microM eicosapentaenoic acid for 2-5 min markedly increased the strength of the depolarizing current required to elicit an action potential (from 18.0 +/- 2.4 pA to 26.8 +/- 2.7 pA, P < 0.01) and the cycle length of excitability (from 525 ms to 1225 ms, delta = 700 +/- 212, P < 0.05). These changes were due to an increase in the threshold for action potential (from -52 mV to -43 mV, delta = 9 +/- 3, P < 0.05) and a more negative resting membrane potential (from -52 mV to -57 mV, delta = 5 +/- 1, P < 0.05). There was a progressive prolongation of intervals between spontaneous action potentials and a slowed rate of phase 4 depolarization. Other polyunsaturated fatty acids--including docosahexaenoic acid, linolenic acid, linoleic acid, arachidonic acid, and its nonmetabolizable analog eicosatetraynoic acid, but neither the monounsaturated oleic acid nor the saturated stearic acid--had similar effects. The effects of the fatty acids could be reversed by washing with fatty acid-free bovine serum albumin. These results show that free polyunsaturated fatty acids can reduce membrane electrical excitability of heart cells and provide an electrophysiological basis for the antiarrhythmic effects of these fatty acids.     

Effect of molecular charge on para- and transcellular access of horseradish peroxidase into rat bile

The permeability pathway into the biliary tree for small inert molecules exhibits a charge selectivity. Using a method which distinguishes trans- from paracellular access, we have examined the charge selectivity of biliary access pathways for the 40-kD protein horseradish peroxidase (pI 7.5), which was derivatized to strongly anionic (pI less than 3.5) and strongly cationic (pI greater than 9.5) isoenzymes. Each isoenzyme was injected as a bolus into the perfusate of an isolated rat liver perfused in situ with a nonrecirculating Krebs-Ringer buffer. Bile was collected at intervals and horseradish peroxidase activity was measured. Its appearance allowed differentiation of paracellular from transcellular access, and the amount entering via each pathway was quantified. The species of enzyme entering bile was the same as that injected as determined by cation-exchange high-performance liquid chromatography of biliary horseradish peroxidase. Paracellular biliary access of anionic horseradish peroxidase was less than 50% that of neutral and cationic horseradish peroxidase both in the control state and when paracellular entry was augmented with 10(-10) M vasopressin. Transcellular access of anionic horseradish peroxidase was similarly restricted. To determine whether this restriction of anionic transcellular access was brought about by diminished hepatocellular uptake or augmented catabolism, we studied these parameters in 4-hr primary hepatocyte cultures. The uptake rates of all species were similar. Little or no degradation or efflux of any horseradish peroxidase species occurred over 30 min in the cultured cells. We conclude that access is charge selective for macromolecules and that this selectivity holds for trans- as well as for paracellular pathways.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fatty acid binding protein in kidney of normotensive and genetically hypertensive rats

Fatty acid binding protein was purified from renal medulla, and its binding activity and fatty acid composition were determined in spontaneously hypertensive stroke-prone rats (SHRSP). Wistar-Kyoto rats (WKY) were used as controls. Fatty acid binding activity was higher in 5-week-old prehypertensive SHRSP than in control WKY (0.155 +/- 0.006 vs 0.030 +/- 0.001 mol palmitic acid/mol protein). However, in 40-week-old rats, the activity was decreased only in SHRSP with established hypertension (0.035 +/- 0.002 vs 0.028 +/- 0.003 mol palmitic acid/mol protein WKY). Fatty acid compositions were similar among 5-week-old and 40-week-old control WKY and 5-week-old SHRSP (palmitic acid, 24%; stearic acid, 14%; oleic acid, 30%; linoleic acid, 29%; arachidonic acid, 3%), although the total amount of bound long-chain fatty acids was decreased in 5-week-old SHRSP, explaining the high fatty acid binding activity in this preparation. Fatty acid binding protein from 40-week-old SHRSP had an elevated proportion of endogenous arachidonic acid, with other fatty acids being relatively reduced (palmitic acid, 8%; stearic acid, 2%; oleic acid, 4%; linoleic acid, 10%; arachidonic acid, 76%), indicating increased arachidonic acid transport in the cytosol. These results show that genetically hypertensive rats had an alteration in fatty acid transport mediated by fatty acid binding protein; this alteration may be involved in the pathogenesis of hypertension.     

Intake of total omega-3 fatty acids,eicosapentaenoic acid and docosahexaenoic acid and risk of coronary heart disease in the Spanish EPIC cohort study

Background and aimsThe evidence about the benefits of omega-3 fatty acid intake on coronary heart disease (CHD) is not consistent. We thus aimed to assess the relation between dietary intake of total omega-3 fatty acids (from plant and marine foods) and marine polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on the risk of CHD in the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC).Methods and resultsThe analysis included 41,091 men and women aged 20–69 years, recruited from 1992 to1996 and followed-up until December 2004. Omega-3 fatty acid intake was estimated from a validated dietary questionnaire. Only participants with definite incident CHD event were considered as cases. Cox regression models were used to assess the association between the intake of total omega-3 fatty acids, EPA or DHA and CHD. A total of 609 participants (79% men) had a definite CHD event. Mean intakes of total omega-3 fatty acids, EPA and DHA were very similar in the cases and in the cohort, both in men and women. In the multivariate adjusted model, omega-3 fatty acids, EPA and DHA were not related to incident CHD in either men or women. The hazard ratios (HR) for omega-3 were 1.23 in men (95% CI 0.94–15.9, p = 0.20); and 0.77 in women (95% CI 0.46–1.30, p = 0.76).ConclusionIn the Spanish EPIC cohort, with a relatively high intake of fish, no association was found between EPA, DHA and total omega-3 fatty acid intake and risk of CHD.     

Inhibitory effects of n-3 polyunsaturated fatty acids on sigmoid colon cancer transformants

Various types of polyunsaturated fatty acids (PUFAs) have been suggested to exert different effects on the colon in terms of promotion or inhibition of tumor development. Results of in vitro and in vivo studies are, however, inconsistent and it remains unclear whether or not the cellular effects of PUFAs change along with the malignant transformation of colonic cells. In this study, we used the NIH3T3 cell line and its SIC (sigmoid colon cancer) oncogene transformants to compare the effects of PUFAs on the proliferation of non-malignant and malignant cells. We also determined the cellular utilization of fatty acids in media by a high-performance liquid chromatography method. The addition of exogenous arachidonic acid (ARA, an n-6 fatty acid), eicosapentaenoic acid (EPA, n-3), and docosahexaenoic acid (DHA, n-3) exerted different effects on NIH3T3 cells, and on SIC transformants, in which selective inhibitory effects were observed at media concentrations ranging from 10 to 20 μg/ml. In cells cultured in media supplemented with EPA or DHA at a concentration of 2 μg/ml, which had no effect on cell proliferation, the cellular utilization of linoleic acid (n-6), a precursor of n-3 fatty acids, was inhibited. This inhibition was stronger in SIC transformants than in NIH3T3 cells (P < 0.05). There was no difference in the utilization of fatty acids between the two cell lines cultured in media supplemented with ARA. We conclude that the cellular response to exogenous long-chain PUFAs is modified during the course of malignant transformation, and that EPA and DHA (n-3 PUFAs) appear to have specific inhibitory effects on cancer cells and may thus enhance the host defense against colon cancer. (Received Dec. 10, 1996; accepted July 25, 1997)     

Understanding omega-3's

Omega-3 fatty acids are a subset of polyunsaturated fatty acids found in marine sources as eicosapentaenoic acid and docosahexaenoic acid and in some leafy vegetables, nuts, and oils as alpha-linolenic acid (ALA). The metabolism of omega-3's may explain the cardioprotective effects observed in epidemiologic and experimental studies. Although most data for cardioprotective effects come from studies of marine sources, vegetable sources of omega-3 fatty acids (alpha-linolenic acid) may have similar effects through in vivo conversion to eicosapentaenoic acid and docosahexaenoic acid. This document will provide an overview of omega-3 fatty acids with a focus on specific sources, metabolism, safety issues, and their potential indication for cardiovascular prevention.     

Diet,fatty acids,and regulation of genes important for heart disease

Diets rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs), such as alpha-linoleic acid, eicosapentaenoic acid, and docosahexaenoic acid, are associated with decreased incidence and severity of coronary heart disease. Similarly, conjugated linoleic acids (CLAs), which are found in meat and dairy products, have beneficial effects against atherosclerosis, diabetes, and obesity. The effects of n3-PUFAs and CLAs are in contrast to fatty acids with virtually identical structures, such as linoleic acid and arachidonic acid (ie, n-6 PUFAs). This article discusses the possibility that cognate receptors exist for fatty acids or their metabolites that are able to regulate gene expression and coordinately affect metabolic or signaling pathways associated with coronary heart disease. Three nuclear receptors are emphasized as fatty acid receptors that respond to dietary and endogenous ligands: peroxisome proliferator activated receptors, retinoid X receptors, and liver X receptors.     

Serotonin fails to induce proliferation of endothelial cells preloaded with eicosapentaenoic acid and docosahexaenoic acid.

Diets rich in fish oils are associated with a reduced risk of cardiovascular disease including reduction of atherosclerosis and restenosis. We examined the effect of omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), major components of fish oils, on serotonin (5HT) stimulated vascular endothelial cells proliferation as a possible mechanism for this vascular protective effect. In this study we demonstrate that 5HT, a known mitogen for vascular endothelial cells, failed to stimulate proliferation of endothelial cells pre-incubated with EPA and DHA. This inhibitory effect was specific for omega-3 fatty acids only and not shared by other fatty acids like oleic acid (monounsaturated) or arachidonic acid (polyunsaturated) or palmitic acid (saturated). When endothelial cells were exposed to EPA and DHA in the ratio present in fish oils, EPA and DHA were shown to act synergistically in inhibiting the proliferative effect of 5HT. These results suggests that one of the mechanisms by which fish oils may confer vascular protective effect is by making the endothelial cells less responsive to mitogenic stimuli of growth factors such as 5HT that are released by aggregating platelets at sites of vascular injury. This inhibition of endothelial cell proliferation may account for the clinically observed effects of fish oil in attenuating the progression of atherosclerotic changes or neointimal proliferation following vascular injury.     

Fatty acid composition of serum lipids in patients with a coronary bypass operation

The fatty acid composition of serum phospholipids and cholesteryl esters was analysed in 71 male patients with angiographically defined three-vessel coronary artery disease (CAD) selected for a coronary bypass operation. Their 71 control subjects were matched according to age, sex, smoking, relative weight, and absence of CAD. The concentrations of fatty acids, 14:0, 16:0 and 16:1 of the serum phospholipids, were significantly (P less than 0.01, P less than 0.05 and P less than 0.01, respectively) higher in CAD patients than in the controls. On the other hand, linoleic (18:2 omega 6), linolenic (18:3 omega 3) and arachidonic (20:4 omega 6) acids were at a significantly lower level in the patients when compared to the controls. The polyunsaturated/saturated fatty acids (P/S) ratio in serum phospholipids was significantly (P less than 0.01) lower in the patients than in the controls. In the cholesteryl ester fraction the results paralleled those of the phospholipids. Significant correlations were obtained between the polyunsaturated fatty acids and the high density lipoprotein cholesterol or apolipoprotein A-I in the control subjects but most of these correlations were absent in the patients. Our present results further support the importance of linoleic acid in the protection against atherosclerosis. However, no unequivocal evidence on the possible beneficial effect of long-chain omega 3-fatty acids in comparison with omega 6-acids was obtained.     

Fat food for a bad mood. Could we treat and prevent depression in Type 2 diabetes by means of ω‐3 polyunsaturated fatty acids? A review of the evidence

AIMS: Evidence strongly suggests that depression is a common complication of Type 2 diabetes mellitus. However, there is considerable room to improve the effectiveness of pharmacological antidepressant agents, as in only 50-60% of the depressed subjects with diabetes does pharmacotherapy lead to remission of depression. The aim of the present paper was to review whether polyunsaturated fatty acids (PUFA) of the omega-3 family could be used for the prevention and treatment of depression in Type 2 diabetes. METHODS: MEDLINE database and published reference lists were used to identify studies that examined the associations between omega-3 PUFA and depression. To examine potential side-effects, such as on glycaemic control, studies regarding the use of omega-3 supplements in Type 2 diabetes were also reviewed. RESULTS: Epidemiological and clinical studies suggest that a high intake of omega-3 PUFA protects against the development of depression. There is also some evidence that a low intake of omega-3 is associated with an increased risk of Type 2 diabetes, but the results are less conclusive. Results from randomized controlled trials in non-diabetic subjects with major depression show that eicosapentaenoic acid is an effective adjunct treatment of depression in diabetes, while docosahexanoic acid is not. Moreover, consumption of omega-3 PUFA reduces the risk of cardiovascular disease and may therefore indirectly decrease depression in Type 2 diabetes, via the reduction of cardiovascular complications. CONCLUSIONS: Supplementation with omega-3 PUFA, in particular eicosapentaenoic acid, may be a safe and helpful tool to reduce the incidence of depression and to treat depression in Type 2 diabetes. Further studies are now justified to test these hypotheses in patients with Type 2 diabetes.     

Fatty acids and epithelial permeability: effect of conjugated linoleic acid in Caco-2 cells

Conjugated linoleic acid (CLA) is a collective term referring to the positional and geometric isomers of linoleic acid. This novel fatty acid has been shown to have a number of beneficial actions, including immunomodulatory, anticarcinogenic, and antiatherogenic effects. Tight junctions of epithelial cells determine epithelial membrane integrity and selective paracellular permeability to ions and macromolecules. Occludin and ZO-1 are integral structural components of the tight junction, which are involved in the biogenesis and functional integrity of the epithelial monolayer. This study investigated the effects of two isomers of CLA (cis-9 and trans-10 isomers) on Caco-2 cell transepithelial resistance (TER) development, paracellular epithelial permeability, and occludin and ZO-1 expression. Caco-2 cells were grown in media supplemented with 0.05 mM linoleic acid, cis-9 CLA, or trans-10 CLA for 21 days. The trans-10 CLA isomer delayed Caco-2 cell TER development, which is an in vitro measure of epithelial cell integrity, and increased paracellular epithelial permeability. Immunofluorescent staining of Caco-2 cell epithelial monolayers grown in media supplemented trans-10 CLA showed that the trans-10 CLA isomer altered distribution of occludin and ZO-1. The trans-10 CLA isomer delayed the acquisition of transepithelial resistance and altered the cellular distribution of occludin, which have important implications in relation to epithelial permeability.     

Chemically defined structured lipids: current status and future directions in gastrointestinal diseases

Over the past two decades various concepts for the supply of lipids in parenteral and enteral nutrition have been developed. Traditionally, the nutritional dietary management typically includes physical mixtures of medium chain and long-chain triglycerides. Recently, chemically defined structured lipids have been developed that combine the advantages of conventional fats with those of special purposes. The first structured lipids were produced by mixing pure medium-chain triglycerides and long-chain triglycerides, allowing hydrolysis to free fatty acids, followed by random transesterification of the fatty acids into mixed triglyceride molecules. This results in a triglyceride containing combinations of short-, medium-, and long-chain fatty acids on a single glycerol backbone. These have unique chemical, physical, and/or physiological properties which differ from simply blending mixtures from the starting fats. By use of 1,3-specific or 2-specific lipases it is now possible to synthesize 1,3-specific or 2-specific triglycerides containing short- and/or medium-chain acids. For instance, incorporation of linoleic, arachidonic, or eicosapentaenoic acid at the sn-2 position is being evaluated for the specific objective of modulating membrane fatty acid composition and essential fatty acid absorption in models of cancer, burns, and immune dysfunction. This contribution reviews the current status of experimental and clinical studies of chemically defined structured lipid-based fat emulsions, with emphasis on their therapeutic potential for nutritional support in hospitalized patients. Accepted: 3 March 1999